PROJECT SUMMARY Adolescence is a critical period for normal, healthy development but also for the onset of significant health problems, including those related to the obesity epidemic such as sleep disordered breathing (SDB). While obesity is highly persistent since childhood, the natural course of childhood SDB is remission in the transition to adolescence. However, the incidence of SDB dramatically increases in adolescence and cohort studies in adults have shown that the association of SDB with adverse cardiometabolic and neurocognitive outcomes is strongest in young adults (20-30y). We hypothesize that the impact of obesity and SDB on adverse health outcomes in young adults is a consequence of their chronic course in the transition from adolescence. From a mechanistic perspective, however, the association of obesity and SDB with these adverse health outcomes remains poorly understood. Likely candidates, beyond standard measures such as waist circumference or number of apneas/hypopneas during sleep, are chronic low-grade inflammation and activation of both limbs of the stress system. There are no prospective studies examining the impact and underlying mechanisms of adolescent obesity and SDB on adverse health outcomes in young adulthood. We propose to conduct a follow- up examination of the Penn State Child Cohort (PSCC), a population-based sample of children who were 5-12 years old at baseline (visit 1) and 12-23 years old at their previous follow-up (visit 2). The overall objective is to prospectively assess the subclinical and clinical consequences of adolescent SDB and obesity and their underlying systemic (immune and stress) mechanisms and lifestyle risk factors. Specifically, we propose to 1) Detail the natural history of SDB in the transition between adolescence and young adulthood and establish its key determinant, focusing on visceral adiposity independent of body mass index percentile; 2) Test the longitudinal association between adolescent SDB with adverse cardiometabolic and neurocognitive outcomes in young adulthood and its underlying immune- and stress-related mechanisms; and 3) Test the longitudinal association between adolescent visceral obesity, independent of SDB, with cardiometabolic and neurocognitive outcomes in young adulthood via systemic mechanisms and novel circadian- and sleep-related lifestyle risk factors. This innovative, transdisciplinary paradigm will fill the gap in current knowledge of the underlying mechanisms playing a key role in the association of adolescent SDB and obesity with adverse health outcomes in young adulthood, while testing two non-mutually exclusive mechanisms as they relate to systemic dysregulation and lifestyle factors. The potential for circadian and sleep disorders to play a role in the association of obesity, a public health problem of epidemic proportions, with adverse health outcomes makes this proposal translational to public health and clinical interventions, as most of the factors and mechanisms explored herein are modifiable. Early prevention at the onset of these highly chronic conditions needs to be supported by a thorough understanding of lifestyle and biological mechanisms.